Toluene → 4-(3-Bromo-2-chloropyridin-4-yl)benzonitrile

Participants

Reaction Conditions

Reaction Steps

A suspension of impure 3-bromo-2-chloro-4-iodopyridine (2.23 g), 4-cyanophenylboronic acid (1.62 g, 11.0 mmol), 2 M aqueous Na2CO3 solution (6 mL, 12 mmol), and toluene (40 mL) was purged with argon, then (Ph3P)4Pd (1.1 g, 0.95 mmol) was added in one portion. The resulting yellow mixture was vigorously stirred under argon at 100° C. for 4 h. Analysis by HPLC/MS indicated the reaction was not complete, and additional 4-cyanophenylboronic acid (0.82 g, 5.57 mmol), 2 M aqueous Na2CO3 solution (3.5 mL) and (Ph3P)4Pd (850 mg) were added. The reaction mixture was stirred at 100° C. for 12 h more. Additional (Ph3P)4Pd (1.0 g) was added, and the reaction mixture was stirred for another 20 h. After cooling to room temperature, the reaction mixture was diluted with water and extracted with EtOAc (40 mL×3). The combined EtOAc extracts were washed with water, then saturated aqueous NaCl, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified using a silica gel cartridge (80 g) eluted with a gradient of EtOAc (0-60%) in hexanes to obtain 590 mg (29%) of the title compound as an off-white solid. HPLC/MS: retention time=3.11 min, [M+H]+=292.

Provenance & Evidence